title: Using laser microporation to improve transdermal delivery of diclofenac: Increasing bioavailability and the range of therapeutic applications.
abstract: The objective of the study was to investigate the effect of laser microporation, using P.L.E.A.S.E.® technology, on diclofenac delivery kinetics. Skin transport of diclofenac was studied from aqueous solution, propylene glycol and marketed formulations across intact and laser-porated porcine and human skins; cumulative permeation and skin deposition were quantified by HPLC. After 24h, cumulative diclofenac permeation across skins with 150, 300, 450 and 900 shallow pores (50-80 μm) was 3.7-, 7.5-, 9.2- and 13-fold superior to that across untreated skin. It was also found to be linearly dependent on laser fluence; Permeation (μg/cm(2))=11.35*Fluence (J/cm(2))+352.3; r(2)=0.99. After 24h, permeation was 539.6 ± 78.1, 934.5 ± 451.5, 1451.9 ± 151.3 and 1858.6 ± 308.5 μg/cm(2), at 22.65, 45.3, 90.6 and 135.9 J/cm(2), respectively. However, there was no statistically significant effect of laser fluence on skin deposition. Diclofenac delivery from marketed gel formulations was also significantly higher across laser-porated skins (e.g. for Solaraze, cumulative permeation after 24h across treated (900 pores/135.9 J/cm(2)) and untreated skin was 974.9 ± 368.8 and 8.2 ± 3.8 μg/cm(2), respectively. Diclofenac delivery from Solaraze across laser-porated porcine and human skins was also shown to be statistically equivalent. The results demonstrated that laser microporation significantly increased diclofenac transport from both simple and semi-solid formulations through porcine and human skin and that pore depth and pore number could modulate delivery kinetics. A similar improvement in topical diclofenac delivery in vivo may increase the number of potential therapeutic applications.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland.
authors.forename: Yogeshwar G
authors.initials: YG
authors.lastname: Bachhav
authors.forename: Arne
authors.initials: A
authors.lastname: Heinrich
authors.forename: Yogeshvar N
authors.initials: YN
authors.lastname: Kalia
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004423:Ear; D006801:Humans; D007834:Lasers; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac